Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is classified according to cause into nociceptive pain, neuropathic pain and psychogenic pain. As pain caused by an unknown cause, fibromyalgia syndrome is known.
Neuropathic pain is pathological pain caused by peripheral or central nervous system dysfunction, more specifically, pain caused by e.g., direct damage and oppression of the nerve tissue despite of no nociceptive stimulus to a nociceptor. As a therapeutic agent for neuropathic pain, an anticonvulsant, an antidepressant, an anxiolytic drug or an antiepileptic drug (gabapentin, pregabalin or the like) is used.
Fibromyalgia syndrome is a disorder in which systemic pain is the leading symptom and neuropsychiatric and neurovegetative symptoms are the secondary symptoms. As therapeutic agents for fibromyalgia syndrome, pregabalin, which has been approved in the United States and Japan, duloxetine and milnacipran, which have been approved in the United States, are principally used. Also, drugs not approved as a therapeutic agent for fibromyalgia syndrome, i.e., a nonsteroidal anti-inflammatory agent, an opioid compound, an antidepressant, an anticonvulsant and an antiepileptic drug are used. However, nonsteroidal anti-inflammatory agents and opioid compounds are generally said to have a low therapeutic effect (Pain and Therapy, Vol. 2, p. 87-104, 2013).
Other than these, French Patent 2 567 885 discloses that substituted piperidines have a cardiotonic activity. JP Patent Publication (Kokai) No. 2006-008664 discloses that imidazole derivatives have an FXa inhibitory effect. International Publication WO 2003/031432 discloses that substituted piperidines have a potential drug efficacy against overweight or obesity. International Publication WO 2013/147160 discloses that an imidazole derivative has an analgesic action.
However, as therapy with a conventional therapeutic agent for neuropathic pain is highly frequently associated with central nervous system adverse effects (e.g., dizziness, nausea or vomiting), long-term administration is difficult. Thus, development of a novel therapeutic agent for neuropathic pain has been desired.
Pregabalin, duloxetine and milnacipran, which have been approved as therapeutic agents for fibromyalgia syndrome, fail to provide a clinically satisfactory therapeutic effect against fibromyalgia syndrome and their drug efficacy significantly varies among patients. In the context, it has been strongly desired to develop a novel therapeutic agent for fibromyalgia syndrome having a sufficient therapeutic effect.
Further, FR '885 suggests that the substituted piperidines described therein have an efficacy for migraine and WO '160 discloses that the imidazole derivative described therein has an analgesic action. However, neither disclosure of the cyclic amine derivative having an analgesic action nor suggestion on the relevancy of an analgesic action to a chemical structure is provided. JP '664 describes imidazole derivatives and WO '432 describes substituted piperidines. Neither disclose nor suggest analgesic action of their respective compounds.
Thus, it could be helpful to provide a compound having a strong analgesic action for pain, in particular, neuropathic pain and/or fibromyalgia syndrome.